This invention relates to aqueous preparations containing an antiallergic drug. More particularly, it relates to aqueous preparations, such as nasal drops, eye drops and paints, i.e. medication paints, containing 9-methyl -3-(1H-tetrazol-5-yl) 4H-pyrido[1,2-a]pyrimidin-4-one potassium salt (hereinafter referred to as TBX). ##STR1##
TBX is the compound described in Japanese Pat. Publication No. 50197/' 85 (corresponding to U.S. Pat. No. 4,122,274) and is known to be effective in suppressing or preventing various symptoms of allergic reactions such as allergic bronchial asthma and allergic rhinitis. It is described in the literature that TBX has an inhibitory effect on a model for type I allergic reaction and suppresses the release of chemical mediators such as histamine and SRS-A (slow reacting substance of anaphylaxis) (Allergy, 33(9), p. 727 & 728, 1984). It is also described in the literature that TBX is useful for the treatment of gastritis and gastric ulcer owing to its protective effect on gastric cells (Gastroenterology, 88(5), p. 1354, 1985).
At present, commercially available antiallergic agents of the chemical mediator release suppression type are predominantly in the form of oral preparations which have systemic action for their object. However, this dosage form cannot necessarily be considered to be most suitable for patients (particularly infants) with allergic rhinitis, ophthalmia or dermatitis, partly because the incidence of side effects is rather high. Accordingly, it may safely be said that, in order to reduce the incidence of side effects and produce the drug effect more efficiently, useful dosage forms are topical preparations such as nasal drops for allergic rhinitis, eye drops for allergic ophthalmia, and paints for allergic dermatitis.
The primary object of the present invention is to provide aqueous preparations, such as nasal drops, eye drops and paints, i.e. medication paints, containing TBX which is an antiallergic agent.
Aqueous preparations must meet the requirements that they are sterile, they contain no foreign matter, the tonicity and pH thereof are not very different from those of the body fluid present at the site of application, no irritation is caused to the site of application, and they are physicochemically stable during long-term storage.
Although TBX is a water-soluble substance, aqueous solutions of TBX have poor storage stability because crystals tend to precipitate therefrom. For example, precipitation of crystals occurred in 10 days when the concentration of TBX was in the range of 0.02 to 2.0% (w/v), and in 12 days when it was 0.002% (w/v). In order to prevent the precipitation of crystals, solubilizing agents such as polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan fatty acid ester, polyvinyl alcohol and glycerin were added. In all cases, however, precipitation of crystals occurred within 14 days. Moreover, conventional ophthalmic buffer solutions such as Hind-Goyan's, Gifford's and Palitzsch's buffer solutions ["The General Principles of Pharmacy (New Edition)", Nankodo, 1980, pp. 39-41] were used, but no satisfactory result could be obtained. The present inventors confirmed these facts on the basis of experiments conducted by themselves.